The experiments described in this proposal are aimed at understanding the molecular mechanisms of vascular development. This will be accomplished by examining the function of an endothelial cell-cell adhesion molecule, PECAM, in the development of blood vessels. First, the expression of PECAM in a cell culture system that undergoes in vitro vasculogenesis will be examined and compared to PECAM expression in murine yolk sacs. Next, the role of PECAM in vasculogenesis will be explored through disruption of PECAM function in the in vitro system. Finally, the developmental potential of purified PECAM-expressing cells and the effects of characterized substrates on vascular development will be investigated. Since PECAM is predicted to play a major role in the maintenance of vascular integrity, as well as in the extravasation of leukocytes and tumor metastasis, an understanding of PECAM's function in vascular development will help facilitate an understanding of these diverse processes.